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Stimulus-responsive drug/gene delivery system based on polyethylenimine cyclodextrin nanoparticles for potential
Hanieh Mousazadeh1, Esat Bonabi2, Nosratollah Zarghami3
1Department of Hematology and Oncology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran; Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
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Combination therapy through simultaneous delivery of anti-cancer drugs and genes with nano-assembled structure has been proved to be a simple and effective approach for treating breast cancer. In this study, redox-sensitive folate-appended-polyethylenimine-β-cyclodextrin (roFPC) host-guest supramolecular nanoparticles (HGSNPs) were developed as a targeted co-delivery system of doxorubicin (Dox) and Human telomerase reverse transcriptase-small interfering RNA) hTERT siRNA) for potential cancer therapy. The nanotherapeutic system was prepared by loading adamantane-conjugated doxorubicin (Ad-Dox) into roFPC through the supramolecular assembly, followed by electrostatically-driven self-assembly between hTERT siRNA and roFPC/Ad-Dox. The roFPC' host-guest structures allow pH-dependent intracellular drug release in a sustained manner, as well as simultaneous and effective gene transfection. This co-delivery vector displayed combined anti-tumor properties of the Dox-enhanced gene transfection, good water-solubility, and biocompatibility, possesses considerably enhanced hemocompatibility, and especially targets folate receptor-positive cells only at low N/P levels to prompt effective cell apoptosis for cancer treatment.
